Matrix effects and selectivity issues in LC-MS-MS

Matrix effect is the effect on an analytical method caused by all other components of the sample except the specific compound to be quantified. Matrix effects and selectivity issues have long been associated with bioanalytical techniques. However the high incidence of matrix effects in liquid chromatographic tandem mass spectrometric (LC-MS-MS) methods has led to a greater understanding of the factors which contribute to these effects. A number of approaches have been investigated to improve reproducibility and robustness of LC-MS-MS methods that are subjected to matrix effect. The modifications described herein relate to instrumentation and methodological issues and include modified ionisation, ionisation switching, extraction modification and gradient high pressure liquid chromatography (HPLC) techniques and have demonstrated significantly improved robustness of complex bioanalytical methods to avoid matrix-related issues.